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- Solange Peters (Lausanne, Switzerland)
- Ravindran Kanesvaran (Singapore, Singapore)
LBA3_PR - An international randomized trial, comparing post-operative conformal radiotherapy (PORT) to no PORT, in patients with completely resected non-small cell lung cancer (NSCLC) and mediastinal N2 involvement: Primary end-point analysis of LungART (IFCT-0503, UK NCRI, SAKK) NCT00410683
- Cécile Le Pechoux (Villejuif, CEDEX, France)
Abstract
Background
Adjuvant PORT has been controversial since publication of a meta-analysis showing PORT could be deleterious especially in pN0 pN1 pts. However, changes have taken place in the management of stage IIIAN2 NSCLC pts including use of adjuvant chemotherapy (CT), patients’ workup, quality of surgery and radiotherapy. Therefore the role of PORT warranted further investigations in high risk pts.
Methods
LungART is a multi-institutional randomized phase III trial comparing mediastinal PORT (54 Gy/27-30 fractions) to no PORT. Pts were eligible if they were PS 0-2, had a complete resection with nodal exploration, proven N2 disease; prior (neo)-adjuvant CT was allowed. The main end-point was disease-free survival (DFS). 500 pts and 292 events were required to show an improvement in DFS from 30% to 42% with PORT (bilateral test). Secondary endpoints included toxicity, local control, patterns of recurrence, overall survival (OS), second cancers, prognostic and predictive factors of treatment effect.
Results
Between August 2007 and July 2018, 501 patients were randomized after surgery or after CT: 252 pts allocated to PORT, and 249 to CA. Median age was 61 (range=36-85), 66% male, histology: mostly adenocarcinoma (73%) and work-up included PET scan in 91% pts. Most patients received CT (post op 77%, pre-op 18%). Analysis for DFS was performed with a median FU of 4.8 yrs; toxicity evaluated on 487 pts (246 in CA). Early and late Gr 3-5 cardio-pulmonary toxicity was respectively 7 and 20% in PORT vs 3,2 and 7,7 % in CA. DFS hazard ratio was 0.85 (95% CI 0.67; 1.07); p=0.16; median DFS was 30.5 months in PORT arm [24;48] and 22.8 in CA [17;37]; 3-year DFS was 47.1% with PORT vs 43.8% with no PORT. 3-year OS was 66.5% with PORT vs 68.5% with no PORT.
Conclusions
LungART is the first European randomized study evaluating modern PORT after complete resection, in pts selected predominantly with PET scan and having received (neo)adjuvant CT. 3-year DFS was higher than expected in both arms and PORT was associated with a non-statistically significant 15% increase in DFS among stage IIIAN2 pts.
Clinical trial identification
NCT00410683.
Legal entity responsible for the study
Gustave Roussy.
Funding
French National Cancer Institute (INCa), French Health Ministry (PHRC), Gustave Roussy and CRUK grant (A13969).
Disclosure
C. Le Pechoux: Honoraria (institution): Amgen; Honoraria (institution), Advisory/Consultancy: AstraZeneca; Honoraria (institution): Lilly; Honoraria (self): PrimeOncology; Honoraria (institution): Medscape; Honoraria (institution), Advisory/Consultancy: Roche; Honoraria (institution), Advisory/Consultancy: Nanobiotix. F. Barlesi: Honoraria (self), Personal fees: AstraZeneca; Honoraria (self): Bayer; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Boehringer-Ingelheim; Honoraria (self): Eli Lilly Oncology; Honoraria (self): F. Hoffmann-La Roche Ltd.; Honoraria (self): Novartis; Honoraria (self): Merck; Honoraria (self): MSD; Honoraria (self): Pierre Fabre; Honoraria (self): Pfizer; Honoraria (self): Takeda. C. Faivre-Finn: Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Elekta. G. Zalcman: Research grant/Funding (institution): Fondation Roche; Honoraria (self), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Travel/Accommodation/Expenses: BMS; Honoraria (self): MSD; Honoraria (self), Advisory/Consultancy: Inventiva; Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: AbbVie; Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy: Da Volterra. J. Madelaine: Honoraria (self), Dr JM received support: AstraZeneca; Honoraria (self): Chugai Pharma; Honoraria (self): Pfizer; Honoraria (self): Boehringer Ingelheim; Honoraria (self): MSD France; Honoraria (self): Roche SAS; Honoraria (self): Actelion; Honoraria (self): GSK; Honoraria (self): Bristol-Myers Squibb. A. Bardet: Advisory/Consultancy: Roche. All other authors have declared no conflicts of interest.
Invited Discussant LBA3_PR
- Rafal Dziadziuszko (Gdansk, Poland)
Q&A and live discussion
- Solange Peters (Lausanne, Switzerland)
LBA4 - IPATential150: Phase III study of ipatasertib (ipat) plus abiraterone (abi) vs placebo (pbo) plus abi in metastatic castration-resistant prostate cancer (mCRPC)
- Johann S. De Bono (London, United Kingdom)
Abstract
Background
PI3K/AKT and androgen receptor (AR) signalling are dysregulated in mCRPC. PTEN loss (40%-50% of mCRPC) results in activation of AKT, the ipat target, and worse outcomes. Preclinically, dual pathway inhibition has greater antitumor activity than AR inhibition. IPATential150 is a phase III, randomised, double-blind study evaluating the efficacy and safety of adding ipat to abi in asymptomatic or mildly symptomatic pts previously untreated for mCRPC.
Methods
Pts with mCRPC were randomised 1:1 to receive ipat (400 mg/d) + abi (1000 mg/d) + prednisone (5 mg bid) or pbo + abi + prednisone. Coprimary endpoints were investigator-assessed radiographic (r) PFS by PCWG3 criteria in pts with PTEN-loss tumours by immunohistochemistry (IHC; PTEN-loss in ≥ 50% of tumour cells) and in the overall ITT. Secondary endpoints included time to PSA progression, PSA response rate, confirmed ORR (per RECIST 1.1 + PCWG3) in ITT pts and pts with PTEN-loss tumours by IHC, and rPFS in pts with PTEN-loss tumours by next-generation sequencing (NGS).
Results
1101 pts were randomised: 547 to ipat + abi and 554 to pbo + abi. Median follow-up was 19 mo. In PTEN loss by IHC pts, median rPFS was 18.5 mo (95% CI: 16.3, 22.1) with ipat and 16.5 mo (95% CI: 13.9, 17.0) with pbo (HR: 0.77; 95% CI: 0.61, 0.98; P = 0.0335); in ITT pts, rPFS was 19.2 mo (95% CI: 16.5, 22.3) with ipat and 16.6 mo (95% CI: 15.6, 19.1) with pbo (HR: 0.84; 95% CI: 0.71, 0.99; P = 0.0431). Secondary endpoints favoured the combination arm (Table). Serious adverse events (AEs) occurred in 40% and 23% of ipat and pbo pts, respectively; AEs leading to discontinuation of ipat/pbo occurred in 21% and 5%.
Conclusions
In this primary endpoint analysis, ipat + abi as first-line treatment for mCRPC resulted in significantly improved rPFS and antitumor activity vs pbo + abi in pts with PTEN-loss mCRPC, but not in the ITT. The safety profile was in line with known and potential risks. NE, not evaluable. a Descriptive.
PTEN Loss by IHC n = 521 ITT Pbo + abi Ipat + abi Pbo + abi Ipat + abi 261 260 554 547 Median (95% CI), mo 7.6 (6.4, 9.3) 12.6 (10.2, 15.3) 8.4 (7.4, 9.3) 12.9 (10.3, 15.1) Stratified HR (95% CI) 0.69 (0.55, 0.87) 0.73 (0.62, 0.85) 187/261, 72 217/260, 84 418/554, 76 444/546, 81 0.0012a 0.0183a 95/261, 36 73/260, 28 187/554, 34 156/547, 29 HR (95% CI) 0.77 (0.56, 1.04) 0.87 (0.70, 1.08) 37/96 60/99 98/225 122/201 % 39 61 44 61 Difference (95% CI), % 22 (7, 37) 17 (7, 27) 103 105 Median (95% CI), mo 14.2 (10.9, 18.7) 19.1 (13.9, NE) HR (95% CI) 0.65 (0.45, 0.95)
Clinical trial identification
NCT03072238.
Editorial acknowledgement
Medical writing support was provided by Scott Battle, PhD, of Health Interactions and funded by F. Hoffmann-La Roche, Ltd.
Legal entity responsible for the study
F. Hoffmann-La Roche, Ltd.
Funding
F. Hoffmann-La Roche, Ltd.
Disclosure
J.S. de Bono: Advisory/Consultancy, Research grant/Funding (institution), Olaparib in BRCA cancers and Investigator Initiated Trial: AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution), Translational studies: Sanofi; Advisory/Consultancy, Research grant/Funding (institution), Translational studies: Astellas Pharma; Advisory/Consultancy: Pfizer; Advisory/Consultancy, Research grant/Funding (institution), Preclinical studies: Genentech/Roche; Advisory/Consultancy, Translational studies: Janssen Oncology; Advisory/Consultancy: Menarini Silicon Biosystems; Advisory/Consultancy, Research grant/Funding (institution), Preclinical studies: Daiichi Sankyo; Advisory/Consultancy, Research grant/Funding (institution), Preclinical studies: Sierra Oncology; Advisory/Consultancy, Research grant/Funding (institution), Preclinical studies: Bayer; Advisory/Consultancy, Research grant/Funding (institution), Preclinical studies: Merck Sharp & Dohme; Advisory/Consultancy, Research grant/Funding (institution), Preclinical studies: Merck Serono; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy, Research grant/Funding (institution), Preclinical studies: Celgene; Advisory/Consultancy, Research grant/Funding (institution), Preclinical studies: Taiho Pharmaceuticals; Advisory/Consultancy, Research grant/Funding (institution), Translational studies: Genmab; Advisory/Consultancy, Research grant/Funding (institution), Preclinical studies: GlaxoSmithKline; Advisory/Consultancy, Research grant/Funding (institution), Preclinical studies: Orion Pharma; Advisory/Consultancy: Eisai; Advisory/Consultancy: Bioxcel Therapeutics; Advisory/Consultancy, Preclinical studies: Astex Pharmaceuticals; Research grant/Funding (institution), Preclinical studies: Cellcentric; Research grant/Funding (institution), Preclinical studies: MedImmune; Research grant/Funding (institution), Preclinical studies: Medivation; Research grant/Funding (institution), Investigator initiated trial: Terumo; Non-remunerated activity/ies, I am the Principal Investigator on multiple trials and have been PI on more than 100 trials with multiple Pharma and Biotech partners: Multiple Pharma and Biotech Partners. S. Bracarda: Advisory/Consultancy: Bayer; Advisory/Consultancy: Astellas; Advisory/Consultancy: Janssen; Advisory/Consultancy: Pfizer; Advisory/Consultancy: BMS; Advisory/Consultancy: Roche; Advisory/Consultancy: Ipsen; Advisory/Consultancy: MSD; Advisory/Consultancy: Merck; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: AAA. C.N. Sternberg: Advisory/Consultancy: Pfizer; Advisory/Consultancy: MSD; Advisory/Consultancy: Merck; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Astellas; Advisory/Consultancy: Sanofi/Genzyme; Advisory/Consultancy: Roche/Genentech; Advisory/Consultancy: Incyte; Advisory/Consultancy: Clovis. K.N. Chi: Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): Astellas; Honoraria (self), Research grant/Funding (institution): Janssen; Honoraria (self), Research grant/Funding (institution): Pfizer; Honoraria (self): Daiichi Sanyo; Honoraria (self), Research grant/Funding (institution): Bayer; Honoraria (self), Research grant/Funding (institution): Roche. D. Olmos: Honoraria (institution), Travel/Accommodation/Expenses: Astellas Pharma ; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Bayer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Janssen; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy: Clovis Oncology; Research grant/Funding (institution): Astellas Medivation; Research grant/Funding (institution): Genentech/Roche; Research grant/Funding (institution): Pfizer; Travel/Accommodation/Expenses: Tokai Pharmaceuticals; Travel/Accommodation/Expenses: Ipsen. S. Sandhu: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Amgen; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (institution): Bristol-Myers Squibb; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (institution): Merck; Honoraria (self): Merck Serono; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche/Genentech; Research grant/Funding (institution): AstraZeneca. C. Massard: Advisory/Consultancy: Amgen; Advisory/Consultancy: Astellas Pharma; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Bayer; Advisory/Consultancy: BeiGene; Advisory/Consultancy: Blueprint Medicines; Advisory/Consultancy: BMS; Advisory/Consultancy: Celgene; Advisory/Consultancy: Debiopharm Group; Advisory/Consultancy: Genentech/Roche; Advisory/Consultancy: Innate Pharma; Advisory/Consultancy: Ipsen; Advisory/Consultancy: Janssen; Advisory/Consultancy: Lilly; Advisory/Consultancy: MSD; Advisory/Consultancy: Novartis; Advisory/Consultancy: Orion; Advisory/Consultancy: Pfizer; Advisory/Consultancy: PharmaMar; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Tahio. N. Matsubara: Advisory/Consultancy, Research grant/Funding (institution): Janssen; Advisory/Consultancy, Research grant/Funding (institution): MSD; Advisory/Consultancy, Research grant/Funding (institution): BMS; Advisory/Consultancy: Astellas; Advisory/Consultancy: Janssen; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Bayer; Advisory/Consultancy: Eisai; Advisory/Consultancy: Ipsen; Advisory/Consultancy: Pierre Fabre. B. Alekseev: Speaker Bureau/Expert testimony: Astellas; Speaker Bureau/Expert testimony: AstraZeneca; Speaker Bureau/Expert testimony: Bayer; Speaker Bureau/Expert testimony: BMS; Speaker Bureau/Expert testimony: Eisai; Speaker Bureau/Expert testimony: Ferring; Speaker Bureau/Expert testimony: Janssen; Speaker Bureau/Expert testimony: Ipsen; Speaker Bureau/Expert testimony: MSD; Speaker Bureau/Expert testimony: Pfizer; Speaker Bureau/Expert testimony: Roche; Speaker Bureau/Expert testimony: Sanofi. R. Gafanov: Advisory/Consultancy, Research grant/Funding (institution): Janssen; Advisory/Consultancy, Research grant/Funding (institution): MSD; Advisory/Consultancy, Research grant/Funding (institution): BMS; Advisory/Consultancy: Astellas; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Bayer; Advisory/Consultancy: Eisai; Advisory/Consultancy: Ipsen; Advisory/Consultancy: Pierre Fabre. M. Borre: Advisory/Consultancy: Ferring; Advisory/Consultancy: MSD; Advisory/Consultancy: Bayer; Advisory/Consultancy: Astellas; Research grant/Funding (institution): AstraZeneca. G. Vasconcelos Alves: Research grant/Funding (institution): MSD; Research grant/Funding (institution): BMS; Advisory/Consultancy, Research grant/Funding (institution): Merck-Serono; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Beigene; Research grant/Funding (institution): Ipsen; Advisory/Consultancy: Janssen. J. Garcia: Full/Part-time employment: Roche. M-L. Harle-Yge: Full/Part-time employment: Roche. G. Chen: Shareholder/Stockholder/Stock options, Full/Part-time employment: Genentech. M.J. Wongchenko: Shareholder/Stockholder/Stock options, Full/Part-time employment: Roche/Genentech. C. Sweeney: Advisory/Consultancy, Research grant/Funding (institution): Astellas; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Janssen; Advisory/Consultancy, Research grant/Funding (institution): Dendreon; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Sanofi; Advisory/Consultancy: Genentech; Advisory/Consultancy: GlaxoSmithKline. All other authors have declared no conflicts of interest.
610O - Final overall survival (OS) analysis of PROfound: Olaparib vs physician’s choice of enzalutamide or abiraterone in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair (HRR) gene alterations
- Johann S. De Bono (London, United Kingdom)
Abstract
Background
The phase 3 randomized, open-label PROfound trial (NCT02987543) met its primary endpoint of significantly prolonged radiographic progression-free survival with olaparib vs physician’s choice of enzalutamide or abiraterone (control arm) in pts with mCRPC with progression on prior therapy and alterations in
Methods
Men with mCRPC and disease progression on a prior new hormonal agent (eg enzalutamide or abiraterone) were randomized 2:1 to olaparib or control treatment. Pts could crossover to olaparib upon radiographic disease progression. A prespecified key secondary endpoint was OS in Cohort A, analysed by alpha-controlled stratified log-rank test.
Results
At data cut-off (20 March 2020), median final OS in Cohort A was significantly longer with olaparib than with physician’s choice of enzalutamide or abiraterone (HR 0.69; 95% CI 0.50, 0.97; *0.047 alpha spent at final OS analysis; †Nominal; ‡Censored pts. CI, confidence interval; HR, hazard ratio; OS overall survival
Cohort A Overall population Olaparib n=162 Control n=83 Olaparib n=256 Control n=131 Events, n (%) 91 (56) 57 (69) 160 (63) 88 (67) 12-month 73 61 67 56 18-month 54 42 47 39 Median follow-up (months) 21.9 21.0 20.7 20.5
Conclusions
PROfound is the first phase 3 trial to show a PARP inhibitor benefit in alpha-controlled OS analyses. Despite extensive crossover from the control arm, olaparib conferred a statistically significant and clinically meaningful prolongation of OS vs sequential therapy with enzalutamide or abiraterone in men with mCRPC with progression on prior therapy and alterations in
Clinical trial identification
NCT02987543.
Editorial acknowledgement
Medical writing assistance was provided by Jacqueline Kolston, PhD, from Mudskipper Business, Ltd, funded by AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, U.S.A. (MSD).
Legal entity responsible for the study
AstraZeneca and Merck.
Funding
AstraZeneca and Merck.
Disclosure
J.S. de Bono: Advisory/Consultancy: Astellas Pharma; Advisory/Consultancy, Licensing/Royalties, Patent WO 20 0 5 0 53662 on DNA damage repair inhibitors for treatments of cancer: AstraZeneca; Advisory/Consultancy: Bayer Healthcare; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Daiichi Sankyo Company; Advisory/Consultancy: Genentech; Advisory/Consultancy: GlaxoSmithKline; Advisory/Consultancy, Licensing/Royalties, Patent US560 4213 on 17 substituted steroids useful in cancer treatment: Janssen Global Services; Advisory/Consultancy: Menarini Silion Biosystems; Advisory/Consultancy: Merck; Advisory/Consultancy: Merck Sharp & Dohme; Advisory/Consultancy: Orion Corporation; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Qiagen Sciences; Advisory/Consultancy: Sanofi Aventis US; Advisory/Consultancy: Sierra Oncology; Advisory/Consultancy: Taiho Pharmaceuticals; Advisory/Consultancy: Vertex Pharmaceuticals. J. Mateo: Advisory/Consultancy: Amgen; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy: Janssen Pharmaceuticals; Speaker Bureau/Expert testimony: Astellas Pharma; Advisory/Consultancy, Research grant/Funding (self): AstraZeneca. K. Fizazi: Honoraria (self), Advisory/Consultancy: Amgen; Honoraria (self), Advisory/Consultancy: Astellas; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: AAA; Honoraria (self), Advisory/Consultancy: Bayer; Honoraria (self), Advisory/Consultancy: Curevac; Honoraria (self), Advisory/Consultancy: Essa; Honoraria (self), Advisory/Consultancy: Janssen Biotech; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Orion Corporation; Honoraria (self), Advisory/Consultancy: Sanofi Aventis US. F. Saad: Advisory/Consultancy, Non-remunerated activity/ies: AstraZeneca; Advisory/Consultancy, Non-remunerated activity/ies: Bristol-Myers Squibb; Advisory/Consultancy, Non-remunerated activity/ies: Merck; Advisory/Consultancy, Non-remunerated activity/ies: Pfizer; Advisory/Consultancy, Non-remunerated activity/ies: Myovant; Honoraria (self), Advisory/Consultancy, Non-remunerated activity/ies: Sanofi; Honoraria (self), Advisory/Consultancy, Non-remunerated activity/ies: Janssen; Honoraria (self), Advisory/Consultancy, Non-remunerated activity/ies: Bayer; Honoraria (self), Advisory/Consultancy, Non-remunerated activity/ies: Astellas. N. Shore: Advisory/Consultancy: Amgen; Advisory/Consultancy: Astellas Pharma; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Bayer; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Dendreon Pharmaceuticals; Advisory/Consultancy: Ferring; Advisory/Consultancy: Janssen Global Services; Advisory/Consultancy: Merck; Advisory/Consultancy: MDxHealth; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Tolmar Pharmaceuticals; Advisory/Consultancy: Clovis. S. Sandhu: Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Endocyte; Research grant/Funding (institution): Genentech; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Merck Serono. K.N. Chi: Research grant/Funding (institution): BC Cancer; Honoraria (self), Advisory/Consultancy: Astellas Pharma; Honoraria (self), Advisory/Consultancy: Janssen Pharmaceuticals; Honoraria (self), Advisory/Consultancy: Sanofi; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Bayer; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: Daiichi Sankyo; Honoraria (self), Advisory/Consultancy: Point Biopharma. O. Sartor: Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Advisory/Consultancy: Bayer; Advisory/Consultancy: Invitae; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Clovis Oncology. N. Agarwal: Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Astellas Pharma; Honoraria (self), Advisory/Consultancy: Bayer; Honoraria (self), Advisory/Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy: Clovis Oncology; Honoraria (self), Advisory/Consultancy: CRISPR; Honoraria (self), Advisory/Consultancy: Eisai; Honoraria (self), Advisory/Consultancy: Eli Lilly; Honoraria (self), Advisory/Consultancy: EMD Serono; Honoraria (self), Advisory/Consultancy: Exelixis; Honoraria (self), Advisory/Consultancy: Foundation Medicine; Honoraria (self), Advisory/Consultancy: Genentech; Honoraria (self), Advisory/Consultancy: Janssen Biotech; Honoraria (self), Advisory/Consultancy: Medivation; Honoraria (self), Advisory/Consultancy: Merck; Honoraria (self), Advisory/Consultancy: Nektar Pharma; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: Pharmacyclics LLC (an AbbVie company); Honoraria (self), Advisory/Consultancy: Seattle Genetics. D. Olmos: Advisory/Consultancy, Travel/Accommodation/Expenses: Astellas Pharma; Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen Pharmaceuticals; Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses, Non-remunerated activity/ies: AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Bayer Healthcare; Advisory/Consultancy: Clovis Oncology; Travel/Accommodation/Expenses, Non-remunerated activity/ies: F. Hoffmann-La Roche; Advisory/Consultancy, Non-remunerated activity/ies: Genentech; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Sanofi. A. Thiery-Vuillemin: Advisory/Consultancy: Astellas Pharma; Advisory/Consultancy: Ipsen Pharma SAS; Advisory/Consultancy: Janssen Biotech; Advisory/Consultancy: Novartis; Advisory/Consultancy: Sanofi Aventis US; Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Advisory/Consultancy, Travel/Accommodation/Expenses: F. Hoffmann-La Roche; Advisory/Consultancy, Travel/Accommodation/Expenses: Merck Sharp & Dohme; Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: Janssen Pharmaceuticals. P. Twardowski: Honoraria (self), Speaker Bureau/Expert testimony: Astellas Pharma; Honoraria (self), Speaker Bureau/Expert testimony: Janssen Biotech. M. Ozguroglu: Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen; Honoraria (self), Advisory/Consultancy: Sanofi; Honoraria (self), Advisory/Consultancy: Astellas; Honoraria (self): Novartis; Honoraria (self): Roche; Travel/Accommodation/Expenses: Bristol-Myers Squibb. J. Kang: Shareholder/Stockholder/Stock options, Full/Part-time employment: AstraZeneca. J. Burgents: Full/Part-time employment, Within last 5 years: AstraZeneca; Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck Sharp & Dohme Corporation. C. Gresty: Shareholder/Stockholder/Stock options, Full/Part-time employment: AstraZeneca. C. Corcoran: Shareholder/Stockholder/Stock options, Full/Part-time employment: AstraZeneca. C.A. Adelman: Shareholder/Stockholder/Stock options, Full/Part-time employment: AstraZeneca. M. Hussain: Honoraria (self), Advisory/Consultancy: AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Bayer; Honoraria (self): Daiichi Sankyo; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Genentech; Honoraria (self), Travel/Accommodation/Expenses: Astellas; Honoraria (self): Physicians' Education Resource; Honoraria (self): Projects in Knowledge; Honoraria (self): Sanofi/Genzyme; Honoraria (self): Phillips Gilmore Oncology; Honoraria (self): Research to Practice; Honoraria (self): MLI Peer Review; Research grant/Funding (institution): Prostate Cancer Clinical Trials Consortium. All other authors have declared no conflicts of interest.
Invited Discussant LBA4 and 610O
- Henrik Grönberg (Stockholm, Sweden)
Q&A live discussion
- Solange Peters (Lausanne, Switzerland)
LBA5_PR - Abemaciclib in high risk early breast cancer
- Stephen R. Johnston (London, United Kingdom)
Abstract
Background
Over 90% of patients with breast cancer are diagnosed with early breast cancer (EBC). While many patients with HR+ disease will not recur or have distant relapse with standard therapies, up to 30% of patients whose cancer has high risk clinical and/or pathological features may experience distant relapse, many in the first 2 years. Novel treatment options are needed to prevent early recurrences and development of metastases for these patients. Abemaciclib is an oral, continuously dosed CDK4 & 6 inhibitor approved for use in HR+, HER2- advanced breast cancer (ABC). Efficacy and safety of abemaciclib in ABC supported phase III evaluation in the adjuvant setting.
Methods
monarchE, an open-label, phase III study, included patients with HR+, HER2-, high risk EBC, who completed primary treatment. Patients with ≥4 positive nodes, or 1-3 nodes and at least one of the following: tumor size ≥5 cm, histologic grade 3, or central Ki-67 ≥20%, were eligible, and randomized (1:1) to abemaciclib (150 mg BID for 2 years) plus endocrine therapy (ET) or ET alone. A prespecified interim analysis was planned at ∼293 IDFS events. The primary endpoint was invasive disease-free survival (IDFS) per STEEP criteria. Secondary endpoints included distant relapse-free survival (DRFS), overall survival, and safety.
Results
5,637 patients were randomized. With 323 IDFS events observed in the intent-to-treat population, positive efficacy required a 2-sided p-value <0.0264. Abemaciclib plus ET demonstrated a statistically significant improvement in IDFS versus ET alone (p=.0096, HR: 0.747, 95% CI: 0.598, 0.932), corresponding to a 25.3% reduction in the risk of an IDFS event. The 2-year IDFS rates were 92.2% vs 88.7%, respectively. A similar improvement was observed for DRFS (HR: 0.717, 95% CI: 0.559, 0.920) with 2-year DRFS rates of 93.6% and 90.3%, respectively. Consistent benefit was seen in all prespecified subgroups. The most frequent AEs were diarrhea, neutropenia and fatigue in the abemaciclib arm and arthralgia, hot flush and fatigue in the control arm. Safety was consistent with the known profile of abemaciclib.
Conclusions
Abemaciclib when combined with ET is the first CDK4 & 6 inhibitor to demonstrate a statistically significant improvement in IDFS in patients with HR+, HER2-, high risk EBC.
Clinical trial identification
NCT03155997.
Editorial acknowledgement
Writing assistance provided by Sarah C. Nabinger (Eli Lilly and Company).
Legal entity responsible for the study
Eli Lilly and Company.
Funding
Eli Lilly and Company.
Disclosure
S.R.D. Johnston: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): AstraZeneca; Advisory/Consultancy, Research grant/Funding (self): Eli Lilly and Company; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Pfizer; Advisory/Consultancy, Research grant/Funding (self): Puma Biotechnology; Speaker Bureau/Expert testimony: Eisai; Speaker Bureau/Expert testimony, Research grant/Funding (self): Roche/Genentech. N. Harbeck: Honoraria (self), Advisory/Consultancy: Eli Lilly and Company; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Pfizer. M. Toi: Honoraria (self), Research grant/Funding (institution): Chugai; Honoraria (self), Research grant/Funding (institution): Takeda; Honoraria (self), Research grant/Funding (institution): Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Kyowa-Hakko-Kirin; Honoraria (self), Research grant/Funding (institution): Taiho; Research grant/Funding (institution), Officer/Board of Directors: JBCRG Association; Honoraria (self), Research grant/Funding (institution): Eisai; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Daiichi-Sankyo; Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self): Eli Lilly and Company; Honoraria (self): MSD; Honoraria (self): Genomic Health; Honoraria (self): Novartis; Honoraria (self), Honorarium for advisory meeting: Konica Minolta; Research grant/Funding (institution): Astellas; Honoraria (self), Honorarium for advisory meeting: BMS; Honoraria (self), Research grant/Funding (institution): Shimadzu; Honoraria (self): Yakult; Honoraria (self), Research grant/Funding (institution): Nippon Kayaku; Research grant/Funding (institution): AFI Technologies; Advisory/Consultancy: Athenex Oncology; Officer/Board of Directors: Organization for Oncology and Translational Research; Officer/Board of Directors: Kyoto Breast Cancer Research Network. M. Martin: Honoraria (self), Research grant/Funding (self), Personal fees: Roche; Honoraria (self), Research grant/Funding (self), Personal fees: Novartis; Honoraria (self), Research grant/Funding (self), Personal fees: Puma; Honoraria (self), Travel/Accommodation/Expenses, Personal fees: Eli Lilly and Company; Honoraria (self), Personal fees: GSK; Honoraria (self), Personal fees: AstraZeneca; Honoraria (self), Personal fees: Amgen; Honoraria (self), Personal fees: Taiho Oncology; Honoraria (self), Personal fees: PharmaMar; Honoraria (self), Personal fees: Pfizer; Honoraria (self), Personal fees: Daiichi Sanyo. M. Campone: Advisory/Consultancy, Fees to the institution: AstraZeneca; Advisory/Consultancy, Fees to the institution: Sanofi; Advisory/Consultancy, Fees to the institution: Servier; Advisory/Consultancy, Fees to the institution: AbbVie; Honoraria (self), Advisory/Consultancy: Eli Lilly and Company; Advisory/Consultancy, fees to the institution: Accord; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, Fees to the institution: Pfizer; Advisory/Consultancy: GT1. E.P. Hamilton: Advisory/Consultancy, Research grant/Funding (institution), Advisory board (no Personal compensation accepted): Eli Lilly and Company; Advisory/Consultancy, Research grant/Funding (institution), Advisory board (no Personal compensation accepted): Pfizer; Speaker Bureau/Expert testimony, Research grant/Funding (institution), Speaker's bureau (no Personal compensation accepted): Genentech/Roche; Advisory/Consultancy: Flatiorn Health; Advisory/Consultancy, Research grant/Funding (institution), Consulting (no Personal compensation accepted): Cascadian Therapeutics; Research grant/Funding (institution): Hutchinson MediPharma; Research grant/Funding (institution): OncoMed; Research grant/Funding (institution): MedImmune; Research grant/Funding (institution): StemCentrx; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Curis; Research grant/Funding (institution): Verastem; Research grant/Funding (institution): Zymeworks; Research grant/Funding (institution): Syndax; Research grant/Funding (institution): Lycera; Research grant/Funding (institution): Rgenix; Advisory/Consultancy, Research grant/Funding (institution), Consulting (no Personal compensation accepted): Novartis; Advisory/Consultancy, Research grant/Funding (institution), Consulting (no Personal compensation accepted): Mersana; Research grant/Funding (institution): Taplmmune; Research grant/Funding (institution): BerGenBio; Research grant/Funding (institution): Tesaro; Research grant/Funding (institution): Medivation; Research grant/Funding (institution): Kadmon; Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): Eisai; Research grant/Funding (institution): H3 Biomedicine; Research grant/Funding (institution): Radius Health; Research grant/Funding (institution): Acerta; Research grant/Funding (institution): Takeda; Research grant/Funding (institution): Macrogenics; Research grant/Funding (institution): Immunomedics; Research grant/Funding (institution): FujiFilm; Research grant/Funding (institution): Effector; Research grant/Funding (institution): Syros; Research grant/Funding (institution): Unum; Research grant/Funding (institution): Sutro; Research grant/Funding (institution): Aravive; Research grant/Funding (institution): Deciphera; Research grant/Funding (institution): Clovis; Research grant/Funding (institution): Sermonix; Research grant/Funding (institution): Zenith; Research grant/Funding (institution): Arvinas; Research grant/Funding (institution): ArQule; Research grant/Funding (institution): Torque; Research grant/Funding (institution): Harpoon; Research grant/Funding (institution): Fachon; Research grant/Funding (institution): Orinove; Research grant/Funding (institution): Molecular Template; Research grant/Funding (institution): Seattle Genetics; Advisory/Consultancy, Research grant/Funding (institution), consulting (no Personal compensation accepted): Daiichi; Advisory/Consultancy, Research grant/Funding (institution), consulting (no Personal compensation accepted): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution), consulting (no Personal compensation accepted): Silverback Therapeutics; Advisory/Consultancy, Research grant/Funding (institution), consulting (no Personal compensation accepted): Black Diamond. J. Sohn: Research grant/Funding (institution): MSD; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Eli Lilly and Company; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): GSK; Research grant/Funding (institution): CONTESSA; Research grant/Funding (institution): Daiichi Sankyo. V. Guarneri: Advisory/Consultancy, Speaker Bureau/Expert testimony: Eli Lilly and Compnay; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, Research grant/Funding (institution): Roche. J. Cortés: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Celgene; Advisory/Consultancy: Cellestia; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy: Biothera Pharmaceutical; Advisory/Consultancy: Merus; Advisory/Consultancy: Seattle Genetics; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Daiichi Sankyo; Advisory/Consultancy: Erytech; Advisory/Consultancy: Athenex; Advisory/Consultancy: Polyphor; Honoraria (self), Advisory/Consultancy: Eli Lilly and Company; Advisory/Consultancy: Servier; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Merck Sharp&Dohme; Advisory/Consultancy: GSK; Advisory/Consultancy: Leuko; Advisory/Consultancy: Bioasis; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy: Boehringer Ingelheim; Honoraria (self), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Eisai; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Honoraria (self): Samsung Bioepis; Research grant/Funding (institution): Ariad Pharmaceuticals; Research grant/Funding (institution): Baxalta GMBH/Servier Affaires; Research grant/Funding (institution): Bayer Healthcare; Research grant/Funding (institution): F. Hoffman-La Roche; Research grant/Funding (institution): Guardanth Health; Research grant/Funding (institution): Piqur Therapeutics; Shareholder/Stockholder/Stock options: MedSIR; Research grant/Funding (institution): Puma C; Research grant/Funding (institution): Queen Mary University of London. P. Neven: Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Eli Lilly and Company. F. Boyle: Honoraria (self), Advisory/Consultancy: Eli Lilly and Company; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: Novartis. I. Smith: Full/Part-time employment, Former employee of Eli Lilly and Company: Eli Lilly and Compnay. D. Headley: Shareholder/Stockholder/Stock options, Full/Part-time employment: Eli Lilly and Company; Shareholder/Stockholder/Stock options: Novartis; Shareholder/Stockholder/Stock options: Takeda; Shareholder/Stockholder/Stock options: Varian Medical Systems; Shareholder/Stockholder/Stock options: Utah Medical Products; Shareholder/Stockholder/Stock options: Zoetis; Shareholder/Stockholder/Stock options: Bayer; Shareholder/Stockholder/Stock options: Merck; Shareholder/Stockholder/Stock options: Roche; Shareholder/Stockholder/Stock options: Evgen; Shareholder/Stockholder/Stock options: AstraZeneca; Shareholder/Stockholder/Stock options: Johnson & Johnson; Shareholder/Stockholder/Stock options: Pfizer; Shareholder/Stockholder/Stock options: Varex Imaging; Shareholder/Stockholder/Stock options: Zimmer BioMet; Shareholder/Stockholder/Stock options: Chugai Pharma. R. Wei: Shareholder/Stockholder/Stock options, Full/Part-time employment: Eli Lilly and Company. M. Frenzel: Shareholder/Stockholder/Stock options, Full/Part-time employment: Eli Lilly and Company. J. Cox: Shareholder/Stockholder/Stock options, Full/Part-time employment: Eli Lilly and Company. J. O'Shaughnessy: Advisory/Consultancy: AbbVie; Advisory/Consultancy: Agendia; Advisory/Consultancy: Amgen Biotechnology; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Britol-Myers Squibb; Advisory/Consultancy: Celgene; Advisory/Consultancy: Eisai; Advisory/Consultancy: Genentech; Advisory/Consultancy: Genomic Health; Advisory/Consultancy: GRAIL; Advisory/Consultancy: Immunomedics; Advisory/Consultancy: Heron Therapeutics; Advisory/Consultancy: Ipsen Biopharmaceuticals; Advisory/Consultancy: Jounce Therapeutics; Advisory/Consultancy: Eli Lilly and Company; Advisory/Consultancy: Merck; Advisory/Consultancy: Myriad; Advisory/Consultancy: Novartis; Advisory/Consultancy: Ondonate Therapeutics; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Puma Biotechnology; Advisory/Consultancy: Prime Oncology; Advisory/Consultancy: Roche; Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy: Syndax Pharmaceuticals; Advisory/Consultancy: Takeda. P. Rastogi: Travel/Accommodation/Expenses: Eli Lilly and Company; Travel/Accommodation/Expenses: AstraZeneca; Travel/Accommodation/Expenses: Roche/Genentech. All other authors have declared no conflicts of interest.
Invited Discussant LBA5_PR
- George Sledge (Stanford, IN, United States of America)
Q&A and live discussion
- Solange Peters (Lausanne, Switzerland)